The incidence of prostate cancer, the second leading of cancer deaths in men, appears to be rising, and occurs about 50% more often in Black men than in White men. Although environmental and genetic factors influence prostate cancer risk, little is currently known about specific environmental risk factors and how they interact with individual susceptibility. This application proposes to identify factors associated with prostate cancer in general and also how those factors may contribute to the significantly higher rate in Black men in particular. A case- control study is proposed, investigating 125 men with prostate cancer (50 Black and 75 White) and 250 age- and race-matched community controls. The research will take advantage of the ability of biomarkers to provide individual-specific information on exposure to, effect of, and/or susceptibility to prostate carcinogens. Three sets of biomarkers will be used, each investigating a specific hypothesis. The first hypothesis is that exposure to cadmium increases the risk of prostate cancer, and urinary cadmium concentration will be used as a biomarker of lifetime cadmium exposure. The second hypothesis is that the lower an individual's DNA capacity, the higher his risk of prostate cancer. Inherent DNA repair capacity will be estimated using biomarkers that reflect the net result of recent oxidative damage and inherent repair capacity and that reflect only recent oxidative damage. The third hypothesis is that increased activity of metabolic pathways may convert environmental chemicals and other xenobiotic compounds to carcinogens increase the risk of prostate cancer, using the ratio of parent compound to metabolites in urine as biomarkers of metabolic activity. The results of these biomarker measurements will be analyzed to determine case- control differences. In addition, associations with traditional prostate cancer risk factors will be analyzed for subsets of cases and controls, using the biomarkers of DNA repair capacity and metabolic activity to define men who may be more susceptible to risk factors than the cohort as a whole. This research has the potential to identify factors associated with prostate cancer risk, which would suggest further investigation of specific environmental causes of prostate cancer, which will lead to a better understanding of ways to prevent prostate cancer.